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Optimization of MC903-induced Atopic Dermatitis Mouse Model : Focusing on Reducing the Induction Period and Adverse Effects

MC903으로 유도하는 아토피피부염 생쥐 동물 모델 최적화 : 유발 기간 단축 및 부작용 감소를 중심으로

  • Soyeon Kim (School of Korean medicine, Pusan National University) ;
  • Ji Hyo Lyu (Research Institute of Korean Medicine) ;
  • Hyungwoo Kim (School of Korean medicine, Pusan National University)
  • 김소연 (부산대학교 한의학전문대학원) ;
  • 류지효 (한의과학연구소) ;
  • 김형우 (부산대학교 한의학전문대학원)
  • Received : 2022.11.21
  • Accepted : 2023.02.17
  • Published : 2023.04.25

Abstract

This study was designed to establish an atopic dermatitis (AD) model using MC903 and was conducted to find out the optimal challenge concentration that can cause dermatitis symptoms enough to be experimentally verified while reducing adverse effects such as weight loss. MC903 was treated at concentrations of 2, 3, and 4 nmol/day, and evaluation of skin surface symptoms, water contents, histopathological changes, body weight changes, and spleen/body weight ratio was conducted. In addition, the expression level of thymic stromal lymphopoietin (TSLP) was also observed. In our results, MC903 induced AD skin lesions such as erythema, scab and fissure and lowered skin moisture level significantly. In addition, water holding capacities in the 3 or 4 nmol groups were diminished significantly compared to that in the control group. On the other hand, 4 nmol treatment induced a weight loss of up to 20% compared to control group. Finally, a higher level of TSLP expression was observed in the 3 nmol group than in the 2 nmol group or the 4 nmol group. Taken together, we propose a total 14-day protocol consisting of 3 days of sensitization (2 nmol/day) and 6 days of challenge (3 nmol/day).

Keywords

Acknowledgement

이 성과는 정부 (과학기술정보통신부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구임 (No. 2022R1A2C2091960).

References

  1. Kim EH, Lee BW, Kim EH. A Literal study of the main symptoms of Atopic dermatitis. Journal of Korean Medical classics 2009;22(1):207-28.
  2. Avena-Woods C. Overview of atopic dermatitis. The American journal of managed care 2017;23(8 Suppl):S115-S123.
  3. Kim M, Kim J. Phenotypes and endotypes of atopic dermatitis: Clinical implications. Allergy, Asthma & Respiratory Disease 2020;8(1):9-14 https://doi.org/10.4168/aard.2020.8.1.9
  4. Indra AK. Epidermal TSLP: a trigger factor for pathogenesis of atopic dermatitis. Expert review of proteomics 2013;10(4):309-11. https://doi.org/10.1586/14789450.2013.814881
  5. He R, Geha RS. Thymic stromal lymphopoietin. Annals of the New York Academy of Sciences 2010;1183(1):13-24. https://doi.org/10.1111/j.1749-6632.2009.05128.x
  6. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proceedings of the National Academy of Sciences 2006;103(31):11736-41. https://doi.org/10.1073/pnas.0604575103
  7. Moosbrugger-Martinz V, Schmuth M, Dubrac S. A mouse model for atopic dermatitis using topical application of vitamin D3 or of its analog MC903. Inflammation: Methods and Protocols. 2017:91-106.
  8. Amano H, Negishi I, Akiyama H, Ishikawa O. Psychological stress can trigger atopic dermatitis in NC/Nga mice: an inhibitory effect of corticotropin-releasing factor. Neuropsychopharmacology 2008;33(3):566-73. https://doi.org/10.1038/sj.npp.1301435
  9. Kim HW, Kim KY, Kim BJ, Chiang SY, Do YH, Nam NL, et al. Effects of alcoholic fermentation extracts from ovary and rind of pear on human skin. The Korea Journal of Herbology 2009;24(1):133-9. https://doi.org/10.6116/KJH.2009.24.1.133
  10. Lyu JH, Kim KH, Kim HW, Cho SI, Ha KT, Choi JY, et al. Dangkwisoo-san, an herbal medicinal formula, ameliorates acute lung inflammation via activation of Nrf2 and suppression of NF-κB. Journal of ethnopharmacology 2012;140(1):107-16. https://doi.org/10.1016/j.jep.2011.12.043
  11. Jang S, Kang Y, Kang Y, Oh S, Kim S, Lyu JH, et al. The ethanol extract of Caragana sinica ameliorated skin lesions in mice with contact dermatitis. Pharmacognosy Magazine 2022;18(77):201.
  12. Addor FA, Takaoka R, Rivitti EA, Aoki V. Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity. International journal of dermatology 2012;51(6):672-6. https://doi.org/10.1111/j.1365-4632.2011.05176.x
  13. Knor T, Meholjic-Fetahovic A, Mehmedagic A. Stratum corneum hydration and skin surface pH in patients with atopic dermatitis. Acta dermatovenerologica Croatica: ADC 2011;19(4):242-7.
  14. Oghazian MB, Ataei S, Radfar M. Vitamin D Intoxication with hypercalcemia due to overuse of supplement. Journal of Pharmaceutical Care 2013:114-6.
  15. Kabata H, Flamar A-L, Mahlakoiv T, Moriyama S, Rodewald HR, Ziegler SF, et al. Targeted deletion of the TSLP receptor reveals cellular mechanisms that promote type 2 airway inflammation. Mucosal immunology 2020;13(4):626-36. https://doi.org/10.1038/s41385-020-0266-x
  16. Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? Journal of Investigative Dermatology 1991;96(4):523-6. https://doi.org/10.1111/1523-1747.ep12470233
  17. Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ, McLean WI, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. Journal of Allergy and Clinical Immunology 2014;134(4):818-23. https://doi.org/10.1016/j.jaci.2014.08.005
  18. Kim MR, Woo SE, Shin SO, Hong SM, Yang SY. A study on the distribution of staphylococcus aureus in atopic dermatitis. Journal of the Society of Cosmetic Scientists of Korea 2006;32(2):93-7.